Bicyclomycin (1) is a clinically useful antibiotic. Information gleaned from ongoing studies have provided the basis of our current notions concerning the mode of action of 1. Unfortunately, little is known concerning the drug activation process, the energetics of key steps, and the interaction of the antibiotic with the receptor site(s). In this proposal, a novel hypothesis for the mode of action of bicyclomycin has been advanced. An integrated approach has been outlined for the further understanding of how the drug and the receptor site function. Detailed experiments are also proposed to discern the effects provided by the biological medium in the drug activation and binding process. Knowledge of this general nature is expected to provide the molecular basis for subsequent research in this area, and allow future general drug design to proceed on a less empirical basis.